Mechanism of effect
Mirabegron is a potent and selective agonist for beta-3 adrenergic receptors. Once beta-3 receptors are activated, the detrusor smooth muscle relaxes to allow for a larger bladder capacity. At higher doses (200 mg), there is a potential for mirabegron to activate beta-1 and beta-2 adrenergic receptors.
Pharmacodynamic
Mirabegron increases blood pressure in a dose dependent manner. However, this effect is reversible when mirabegron is discontinued. Mirabegron also increases heart rate in a dose dependent manner.
Pharmacokinetics
Bioavailability: 29% (25-mg), 35% (50-mg)
Peak Plasma Time: 3.5 hr
Peak Plasma Concentration: ~3-fold increase from 50 mg dose to 100 mg dose
AUC: ~2.5-fold increase from 50 mg dose to 100 mg dose
Steady state: 7 days
Protein Bound: 71%
Vd, steady state: 1670 L
Metabolism
Via multiple pathways including dealkylation, (direct) glucuronidation, amide hydrolysis, and minimal oxidative metabolism in vivo by CYP2D6 and CYP3A4
Possible involvement of butylcholinesterase, uridinediphospho-glucuronosyltransferases (UGT) and alcohol dehydrogenase
Moderate CYP2D6 inhibitor
Half-Life: 50 hr
Total body clearance: 57 L/hr (following IV administration)
Excretion: Urine (55%); feces (34%)
Excretion, unchanged: Urine (~25%); feces (0%)
Drug indications
overactive bladderDosage
Adult
Overactive Bladder
- 25 mg PO qDay
- 25 mg dose is typically effective within 8 weeks
- May increase to 50 mg PO qDay based on individual efficacy and tolerability
Pediatric
Safety and efficacy not established
Drug contraindications
HypersensitivitySide effects
Diarrhea , Headache , dry mouth , vertigo , Hypertension , sinusitis , Cystitis , tiredness , tachycardiaInteractions
Dimethyl Fumarate , Pimozide , Thioridazine , Tamoxifen , Eliglustat , Venetoclax , BrexpiprazoleAlerts
May increase blood pressure; monitor blood pressure periodically, especially in hypertensive patients; not recommended for use in severe uncontrolled hypertensive patients (defined as systolic blood pressure ≥180 mm Hg and/or diastolic blood pressure ≥110 mm Hg)
Urinary retention may occur with bladder outlet obstruction or with concomitant antimuscarinic therapy; administer with caution in these patients
Angioedema of the face, lips, tongue, and/or larynx reported; may occur after the first dose or following multiple doses; promptly discontinue and initiate appropriate therapy to ensure a patent airway
Drug interactions overview
- Appropriate monitoring is recommended and dose adjustment may be necessary for narrow therapeutic index CYP2D6 substrates
- Coadministration of digoxin 0.25 mg with a combination of solifenacin 5 mg and mirabegron 50 mg increased digoxin AUC and peak plasma concentration by ~10% and 14%, respectively; for patients who are initiating a combination of mirabegron and digoxin, consider initiating lowest dose for digoxin; monitor serum digoxin concentrations and titrate digoxin dose to obtain the desired clinical effect
- In studies, ketoconazole increased mirabegron peak plasma concentration by 45% and mirabegron AUC by 80% after multiple dose administration of 400 mg of ketoconazole for 9 days prior to the administration of a single dose of 100 mg mirabegron in 23 male and female healthy subjects
Points of recommendation
- It may take several weeks to see the full effects.
- High blood pressure has happened with mirabegron. Have your blood pressure checked as you have been told by your doctor.
- Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using mirabegron while you are pregnant.
- Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.
- Take with or without food.
- Swallow whole. Do not chew, break, or crush.
- Take with a full glass of water.
- Skip the missed dose and go back to your normal time.
- Do not take 2 doses at the same time or extra doses.
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